SU858563A3 - Method of preparing quinazoline derivatives or their salts - Google Patents

Abstract

Process for preparing quinazoline derivatives, of the formula: (Formula) ** wherein (i) R 1 is a hydrogen atom or a lower alkyl group; (R2) n represents from 1 to 3 optional substituents, each R2 being a hydrogen atom or a hydroxy or lower alkoxy group and n being from 1 to 3, or any two of the R2 halves constituting a methylenedioxy or ethylenedioxy group attached to positions adjacent to ring A; (ii) X represents - (CH2) p- wherein p is 1 to 3; (iii) and is attached to the 3 or 4 position of the C ring and represents a group of formula -Z-CO-NHR6 or -Z-CS-NHR6.

Description

(54) METHOD FOR PRODUCING HINAZOLINE DERIVATIVES The invention relates to a method for producing new quinae derivatives of the formulas where Y is NHCONR R, z, NHC S NR R, or CHaCONR R groups where R is a lower alkyl group, a hydroxyalkyl group, an alkyl, alkenyl or quinil, substituted pyridyl. RJ, is hydrogen, and R together with the nitrogen atom to which they are attached form a piperidine ring, X is the group CH2. —CH or when V is CHACON; the group, then the X — group — CH. S., or their salts, which possess biological activity. There is a method of reacting isocyanates with amines ij. The purpose of the invention is a method for the preparation of new quinazoline derivatives, which can be used in OR THEIR SALT as biologically active compounds. The objective is achieved by a process for the preparation of compounds of formula 1, namely, quinoline of the formula NCO, NCS or CftjCOQ, with Q being an easily removable group such as chlorine, bromine or O-o-a. X -, or when Z is CH, .COQ, then X - is reacted with a compound of formula NH, where ft-ji have the specified values in an inert solvent at room temperature and implant the desired product in free form. in the form of salt. The pharmaceutically applicable acid addition salts of the compounds of Formula 1 are those which are derived from acids containing pharmaceutically applicable anions, such as hydrochloride, hydrobromide, hydroxide, sulfate or bisulfate, phosphate or phosphate, acetate, maleate, fum rat, oxalate, lactate, gartrat, citrate, gluconate, saharat and p-goluylsulfonat. Example. 1 / DSSD and N-hydroxysuccinnamide 2 (CH3) CH2) CH, COf {} iiCHg), C CH-COM), CHj4- (4-carboxymethyl) -1,2, 3,6-tetrahydrolirid-1-yl - 6,7-dimethoxychimazoline hydrochloride (0.92 g), obtained by hydrolysis of ether in dry chloroform (20 ml) containing triethylamine (0.3 g), is stirred until the reaction is complete. Dicyclohexyl carbodiimide (0.63 g and N-hydroxysuccinimide (0.35 g) is added, followed by standing overnight, resulting in more solid n-butylamine (0.22 g) precipitating, added to the mixture and again left to stand for 5 hours, then the solution is filtered, washed with water, and the organic phase is evaporated in vacuo to dryness. The residue is treated with acetonitrile, filtered, and the Filtoate is treated with ethereal HCl to form an acidic acid. The precipitated hydrochloride 4-I. N-butylcarbamoylmethyl) -1,2,3,6-tetradidropyrid-1-yl-6,7-dimethoxyquin-; Azoline is recrystallized from eta, nola. Exit 340 mg at 1. as a hemihydrate., Calculated,%: C 58.65, H 7.0, N 13.0. C2i% gN 03-l / 2 HgO Found;%: C, H 6.7; N 12.9. Examples 2-7. Obtaining derivatives of compounds of the formula The results are presented in the table.

2 / NHCONH ((CH3) 4-Put-

 NHCON

The same Dihydrochlo- 136-201 53.39

(53.87

-NHCONH (CH.2) OH

Free base NHCONH (CH,) 2. Free-pyridyl base

Free

NHCONH-CHj CHsCHj, base

6.56 13, 6.68 13.31)

6.61

14.82

15.54) 6.43

131-145 59.54 7.24 17.36 (58.96 7.84 16.97)

211-214 61,446,78 18,85

(61, iJ 6.81 18.85) Monotertrate, 122-135 53.62 (53.39 199-201 63.29 6.47 19.25 (63.26 6.37 18.96)

NHCONHCH C S CH

Monohydrate

197-190 58.90 (59.35

Claims (1)

The invention The method of obtaining quinazoline derivatives of the formula 1 G tf-X-1 2 - NCO, NCS or CH COQ, npHQ groups are easily removed, such as chlorine, bromine ON (D; O where y is NHCONR jR NHCSNR R2 OR CHjiCONR Rg groups, where R is a lower alkyl group C-C oxyalkyl group, alkyl, alkenyl, or alkynyl, substituted with pyridyl; ft is hydrogen, and R together with the nitrogen atom to which they are attached form a piperidine ring X, a CHi-CH group, or, when RZ, then X is a.-CH-C group or their salts, characterized in that quinazoline Formula II, ": X - CH" -CH, Y, or when 2 represents CHjCOQ, then X - is reacted with a compound of formula III - where R and R 2 have the indicated value in an inert solvent at room temperature and leach out in free form or in the form of solts. Sources of information taken into account in the examination 1. Weigand-Hilgetag. Experimental methods in organic chemistry. M., Himi, 1968, p. 377,